Locating Agents in RFID Architectures

The use of software agents can create an “intelligent” interface between users’ preferences and the back‐end systems. Agents are now able to interact and communicate with each other, forming a virtual community and feeding back the user with suggestions. Innovative systems related to Asset Tracking, Inventory and Shelving architectures are more often involving advanced communication techniques (e.g., RFID); these systems are responsible for user authentication and objects verification. RFID systems could have jamming situations where many objects are moving at the same time and in the same direction. Moreover, other disadvantages have also been observed, such as hindering further implementations, privacy and security issues problems, in addition to the system’s disruptive behavior in case of crowd checkouts (e.g., Supermarket and Airports). Addressing these disadvantages, this paper proposes a possible integration between a Multi‐Agent framework and an RFID‐based application (back‐end). This integration would allow objects (such as passports or goods) with RFID tags to better check‐out through airports or supermarket gates that contain RFID‐readers

Simple chromatographic and spectrophotometric determination of sofosbuvir in pure and tablet forms

Two methods, a reversed phase high-performance liquid chromatographic (RP-HPLC) method and a direct ultra-violet spectrophotometric method, were adopted and validated for the quantification of sofosbuvir, which is a new antiviral agent used for treatment of patients with hepatitis C virus (HCV). Validation parameters such as linearity, accuracy, precision, specificity, limits of detection and quantification were determined according to the guidelines of International Conference on Harmonization (ICH)-Q2B. The RP-HPLC method was applied on HypersilTM ODS C18 column (150×4.6 mm, 5 µm) as a stationary phase. The mobile phase was optimized according to the polarity of the studied drug. It was methanol: acetonitrile (90:10, v:v), pumped using an isocratic mode with flow rate of 1 mL/min and UV detection at 260 nm. The UV spectrophotometric method was performed for the studied drug at 260 nm. The calibration curves were linear in the ranges of 2-60 µg/mL and 5-40 µg/mL for the RP-HPLC and UV spectrophotometric methods, respectively. The proposed methods are accurate, sensitive and precise, so they can be successfully adopted for the reliable determination of sofosbuvir content in its tablet form

Validated simultaneous spectrophotometric quantification of a new antiviral combination

Simple, selective and precise spectrophotometric methods were applied for simultaneous quantification of sofosbuvir (SFV) and ledipasvir (LDI) both in their raw and dosage forms. In the first method, the two cited drugs were determined simultaneously using first derivative (D1) method. It was accomplished by measuring peak heights at 275 nm and 344 nm, for SFV and LDI, respectively, in concentration ranges of 5 - 80 μg/mL and 3 - 50 μg/mL, for SFV and LDI, respectively. In the second one, a first derivative of ratio spectra (1DD) method was adopted to quantify SFV in concentration range of 5 - 80 µg/mL. It was adopted by measuring the peak amplitudes (valley and peak) at 259 nm and 280 nm, using 25 µg/mL LDI as a divisor. The proposed method was also used to determine LDI in concentration range of 3 - 50 µg/mL by recording the peak amplitudes (valley and peak) at 319 nm and 375 nm, using 80 µg/mL SFV as a divisor. The developed methods were validated with respect to linearity, accuracy, precision, selectivity, robustness and limits of detection and quantification (LOD and LOQ), as per the guidelines of International Conference on Harmonization (ICH)-Q2B

Assessment of Multi-Story Building Seismic Design Factors with Structural Irregularity

Many high-rise buildings are practically irregular as a result of the architectural and service requirements in the design process, errors and modification during the construction phase, and changes of the building use throughout its service life. Structural irregularities could increase the uncertainties related to the ability of the building to meet the design objectives. This study is thus devoted to assess the safety margins and calibrate the seismic design response factors of modern high-rise buildings with different vertical irregularity features. A brief survey of the most common vertical irregularities inn reinforced concrete multi-story buildings is conducted to select reference structures. Five 50-story high-rise buildings are then selected and fully designed using international building codes to represent well-designed tall buildings with principal vertical irregularity types. Fiber-based simulation models are developed to assess the seismic response of the five benchmark buildings under the effect of forty earthquake records representing far-field and near-field seismic scenarios. The comprehensive results obtained from inelastic pushover and incremental dynamic analyses are employed to provide insights into the local and global seismic response of the reference structures. The probabilistic vulnerability assessment of the five high-rise buildings is conducted at different limit states using fragility relationships. The study concluded that the seismic performance of well-designed regular and vertically irregular high-rise buildings is satisfactory under the design earthquake. Under severe earthquakes, the seismic response of tall buildings with extreme soft story and geometry irregularity is not inferior to that of the regular counterpart at different seismic performance levels. Despite the over strength factor adopted in the design of buildings with discontinuities in the lateral-force-resisting system and extreme weak story, the observed negative impacts of these irregularity categories on increasing the vulnerability of high-rise buildings are substantial. This confirms the pressing need for mitigation strategies to reduce the expected seismic losses of the latter classes of building. The calibration of seismic design response factors of the reference high-rise buildings also confirms that, although the code coefficients are adequately conservative, they can be revised to arrive at a more efficient and cost-effective design of regular and irregular high-rise building

Development and validation of spectrophotometric methods for simultaneous determination of sitagliptin and simvastatin in binary mixture

Simple, selective and precise spectrophotometric methods were adopted for simultaneous determination of sitagliptin (SIT) and simvastatin (SIM) in new co-formulated pharmaceutical dosage form. In the first method, SIT was determined by measuring its zero order absorbance at 266.4 nm in the range of 40-360 µg/mL in the presence of up to 70% of SIM. While, the two cited drugs were determined simultaneously using third derivative method by measuring the sum of peak amplitudes (peak & valley) at 275.3-280.3 nm and 240.5-244.7 nm in the ranges of 40-360 µg/mL and 2-18 µg/mL for SIT and SIM, respectively. In the second method, the first derivative of ratio spectra method was applied by measuring the peak height at 255.9 and 275.2 nm using 18 µg/mL SIM as devisor over a concentration range of 40-360 µg/mL of SIT and at 228.3, 240.5 and 248 nm using 100 µg/mL of SIT as divisor over a concentration range 2-18 µg/mL SIM. In the third method the ratio subtraction spectrophotometric method was used, where SIM can be determined by dividing the spectra of the mixtures by the spectrum of SIT (40 µg/mL) followed by subtracting the constant absorbance value of the plateau, then finally multiply the produced spectrum by the spectrum of the devisor. Laboratory prepared mixtures were successfully tried for the three compositions of tablets (10, 20 and 40 mg of SIM) with 100 mg of SIT. The developed methods were validated as per International Conference of Harmonization guidelines

Simultaneous determination of Simvastatin and Sitagliptin in tablets by new univariate spectrophotometric and multivariate factor based methods

Five simple, sensitive and precise spectrophotometric and chemometric methods were used for simultaneous determination of Simvastatin (SM) and Sitagliptin (SIT) in their pure powdered forms and in the tablets. The proposed methods are the extended ratio subtraction method (EXRSM), ratio difference method (RDSM), mean centering of ratio spectra method (MCR) and chemometric methods, namely principal component regression (PCR) and partial least squares (PLS). In EXRSM; SM was determined at 237.5 nm, while SIT was determined at 267 nm, in RDSM; the difference in amplitudes at 237.5 and 245.5 nm was used for SM and 263.5 and 248.0 nm for SIT, while in MCR; SM and SIT were determined at 239.0 and 273.0 nm, respectively. PCR and PLS are factor based multivariate methods which utilize the whole spectra of SM and SIT. The developed methods were successfully applied for the determination of the studied drugs in their bulk powder, laboratory prepared mixtures and in tablets. All validation parameters of the developed methods were determined. The obtained results were statistically compared with each other along with a reported method

Discovery and optimization of 1,3,5-trisubstituted pyrazolines as potent and highly selective allosteric inhibitors of PKCzeta

The atypical PKCζ is a promising therapeutic target in inflammatory diseases and B cell lymphoma. Therefore, there is an increasing need to develop selective inhibitors for this enzyme without affecting the closely related PKC family members. Allosteric inhibitors were found to be an effective tool in achieving this aim. Optimization yielded the 1,3,5-trisubstituted pyrazoline scaffold which proved to be rich in modifiable sites, all acting as hot spots for improving binding affinity. The phenolic group at the 5-phenyl was essential for activity. The presence of a lipophilic substituent at the 1-phenyl was important for high potency. The 3-position was tolerant for diverse types of substituents, acting as a means to optimize polarity and physicochemical characteristics. A methyl group at the 4-postion of the pyrazoline increased the potency, and was reported to enhance pyrazoline’s chemical stability. The optimized compounds showed two orders of magnitude improvement in the cell free assay potency and more than 10 times increase in cellular potency in U937 cells. The compounds showed high selectivity for PKCζ vs. the closely related PKCɩ and other PKCs, and were most likely targeting the PIF-pocket. Since the pyrazoline scaffold showed shape complementarity also to the p53-Mdm2 interaction site, the ability to compete this other protein-protein interaction was tested. However, the compounds which showed potent growth inhibition in cells failed to show activity in the binding assay.Die atypische PKCζ ist ein vielversprechendes Target bei Entzündungserkrankungen und B-Zell-Lymphomen. Daher besteht ein Bedarf, selektive Inhibitoren dieses Enzyms zu entwickeln, welche eng verwandte PKC-Isoformen nicht hemmen. Allosterische Hemmstoffe stellten gute Ansatzpunkte zum Erreichen dieses Zieles dar. Eine Optimierung führte zu 1,3,5-trisubstituierten Pyrazolinen, die an vielen Positionen vorteilhaft modifiziert werden konnten, was jeweils in einer effektiven Erhöhung der Bindungsaffinität resultierte. Der Phenolrest in der 5-Position war dabei essentiell für die biologische Aktivität. Ebenso war die Anwesenheit eines lipophilen Substituenten am 1-Phenylrest wichtig für eine hohe Potenz. An der 3-Position wurden verschiedene Arten von Substituenten toleriert, so dass hier die Polarität der Verbindungen und weitere physikochemische Eigenschaften optimiert werden konnten. Eine Methylgruppe an der 4-Position des Pyrazolins erhöhte die Wirkstärke zusätzlich und wurde zugleich als stabilisierend auf die chemische Stabilität beschrieben. Die optimierten Hemmstoffe zeigten eine um zwei Größenordnungen höhere Potenz im zellfreien Assay und eine 10-fach bessere Wirksamkeit im U937-Zellassay als die Ausgangsverbindungen. Die Verbindungen besaßen eine hohe Selektivität für PKCζ gegenüber der stark homologen PKCι und weiteren PKC-Isoenzymen, und griffen wahrscheinlich an der PIF-Tasche an. Da das Pyrazolingerüst auch eine Formkomplementarität zur p53-Mdm2-Interaktionsstelle aufwies, wurde die Fähigkeit, diese andere Protein-Protein-Interaktion zu kompetitieren, gestestet. Für diejenigen Verbindungen, die eine potente Hemmung des Zellwachtums zeigten, konnte jedoch keine Aktivität im Bindungsassay nachgewiesen werden